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Principal Investigator: Luu Van Pham
Organization: JOHNS HOPKINS UNIVERSITY
Fiscal Year: 2024
Award: $195,806
Funding agency: National Heart Lung and Blood Institute
PROJECT SUMMARY
Sleep disordered breathing (SDB) is a highly prevalent disease that is associated with increased risk for incident
diabetes. Mechanisms of SDB-induced dysglycemia have not been elucidated. Hypoxemia has been implicated
as a key pathogenic factor in the development of glucose intolerance and diabetes. High altitude populations,
who experience chronic hypoxia, represent unique cohorts to study the role of nocturnal hypoxemia in the
pathogenesis of SDB-related diabetes. Our group previously demonstrated that severity of nocturnal hypoxemia,
independent of daytime oxyhemoglobin saturation, was associated with elevated hemoglobin A1c. To date, no
study has shown that targeting nocturnal hypoxemia improves glucose control.
In this application, we will investigate the hypothesis that nocturnal hypoxemia causes dynamic nocturnal glucose
elevations, that are mitigated by oxygen. We will employ continuous glucose monitoring to examine the temporal
association between glucose and oxygenation dynamics in an observational study and examine the effects of
nocturnal oxygen supplementation in a randomized cross-over study. Successful completion of this proposal will
provide mechanistic proof that nocturnal hypoxia is a reversible cause of dysglycemia in highlanders.
The applicant, Dr. Luu Pham, is a physician in Pulmonary, Critical Care and Sleep Medicine, who seeks to
develop a research career focused on the pathogenesis of SDB-related metabolic diseases. This proposal would
allow the applicant dedicated time to conduct the outlined research project, as well as pursue didactic training in
design and conduct of clinical trials and further quantitative methods relevant to this project and future research
plans. The data generated from this research proposal will form the basis for an R01 application to examine the
impact of treating of hypoxemia in the pathogenesis diabetes. The career development plan for this applicant
includes a structured approach to mentoring, didactic coursework focused on a specific research goal,
participation in local and national meetings and identification and regular assessment of career milestones.
The research environment provided by Johns Hopkins University as well as the mentorship team described in
this application will assist in Dr. Pham’s successful completion of his career and research goals. The Division of
Pulmonary and Critical Care Medicine and Johns Hopkins University have a long history of training successful
young clinical researchers. The pre-existing high-altitude research infrastructure and trained field staff, as well
as the applicant’s established and ongoing collaboration with his team of mentors, will ensure that the study
goals will be completed within the timeframe of this award. We have assembled a mentoring team of established
faculty with distinct, complementary strengths in high altitude research, clinical trials, metabolic sequelae of SDB
and biostatistics, relevant to this proposal. In addition, each member of the mentoring committee serves as an
excellent role model for the applicant’s career development into an independent investigator.
Terms: <Abnormal Assessment of Metabolism><Acute><Address><Adult-Onset Diabetes Mellitus><Air><Altitude><Award><Biometrics><Biometry><Biostatistics><Breathing><CPAP><CPAP Ventilation><Chronic><Clinical><Clinical Trials><Cohort Studies><Collaborations><Concurrent Studies><Conduct Clinical Trials><Continuous Glucose Monitor><Continuous Positive Airway Pressure><Critical Care><Cross-Over Studies><Cross-Over Trials><Crossover Studies><Crossover Trials><D-Glucose><Data><Data Analyses><Data Analysis><Dedications><Development><Development Plans><Dextrose><Diabetes Mellitus><Disease><Disorder><Dose><Ensure><Environment><Exhibits><Exposure to><Faculty><Funding><Glucose><Glucose Intolerance><Glycated Hemoglobins><Glycohemoglobin A><Glycosylated Hemoglobin><Glycosylated hemoglobin A><Goals><Hb A1><Hb A1a+b><Hb A1c><HbA1><HbA1c><Hemoglobin A(1)><History><Home><Hour><Hyperglycemia><Hypoxemia><Hypoxia><Hypoxic><Impairment><Insulin Resistance><Intermediary Metabolism><Intervention><Intervention Strategies><Investigators><Ketosis-Resistant Diabetes Mellitus><Laboratories><Link><Lung><Lung Respiratory System><Maturity-Onset Diabetes Mellitus><Medicine><Mentors><Mentorship><Metabolic><Metabolic Diseases><Metabolic Disorder><Metabolic Processes><Metabolic Studies><Metabolism><Metabolism Studies><Methods><Modeling><NIDDM><NIH><National Institutes of Health><Non-Insulin Dependent Diabetes><Non-Insulin-Dependent Diabetes Mellitus><Noninsulin Dependent Diabetes><Noninsulin Dependent Diabetes Mellitus><O element><O2 element><Observation research><Observation study><Observational Study><Observational research><Oxygen><Oxygen Deficiency><Oxyhemoglobin><Pathogenesis><Pathogenicity><Pathogenicity Factors><Patients><Pattern><Peru><Peruvian><Physicians><Placebos><Population><Pulse Oximetry><R-Series Research Projects><R01 Mechanism><R01 Program><Randomized><Recording of previous events><Research><Research Grants><Research Infrastructure><Research Personnel><Research Project Grants><Research Projects><Research Proposals><Research Training><Researchers><Respiratory Aspiration><Respiratory Inspiration><Risk><Role><Sea><Severities><Sham Treatment><Sleep><Sleep Apnea><Sleep Apnea Syndromes><Sleep Hypopnea><Sleep-Disordered Breathing><Slow-Onset Diabetes Mellitus><Stable Diabetes Mellitus><Stimulus><Structure><Subgroup><Supplementation><T2 DM><T2D><T2DM><Testing><Thesaurismosis><Time><Training><Type 2 Diabetes Mellitus><Type 2 diabetes><Type II Diabetes Mellitus><Type II diabetes><United States National Institutes of Health><Universities><Virulence Factors><Wakefulness><Withdrawal><adult onset diabetes><blood glucose regulation><career><career development><cohort><continuous blood glucose monitor><continuous blood sugar monitor><continuous glucose measurement><continuous sugar monitor><data interpretation><design><designing><developmental><diabetes><diabetes pathogenesis><experience><glucose control><glucose homeostasis><glucose regulation><hemoglobin A1c><histories><homes><hyperglycemic><hypertension control><hypertension management><hypoxemic><improved><inspiration><insulin resistant><insulin tolerance><interstitial><interventional strategy><ketosis resistant diabetes><maturity onset diabetes><meeting><meetings><member><metabolic abnormality assessment><metabolism disorder><meter><nocturnal Hypoxemia><novel><prevent><preventing><pulmonary><randomisation><randomization><randomly assigned><recruit><response><role model><sham therapy><sleep-related breathing disorder><social role><supplemental oxygen><temporal measurement><temporal resolution><time measurement><type 2 DM><type II DM><type two diabetes><volunteer><wearable health monitor><wearable health tracker><wearable monitor>